Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA; Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: ryanjp@upmc.edu.

2

Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.

3

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.

4

Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Abstract

There is converging evidence that insulin plays a role in food-reward signaling in the brain and has effects on enhancing cognition. Little is known about how these effects are altered in individuals with insulin resistance. The present study was designed to identify the relationships between insulin resistance and functional brain connectivity following a meal. Eighteen healthy adults (7 male, 11 female, age: 41-57 years-old) completed a frequently-sampled intravenous glucose tolerance test to quantify insulin resistance. On separate days at least one week apart, a resting state functional magnetic resonance imaging scan was performed: once after a mixed-meal and once after a 12-h fast. Seed-based resting state connectivity of the caudate nucleus and eigenvector centrality were used to identify relationships between insulin resistance and functional brain connectivity. Individuals with greater insulin resistance displayed stronger connectivity within reward networks following a meal suggesting insulin was less able to suppress reward. Insulin resistance was negatively associated with eigenvector centrality in the dorsal anterior cingulate cortex following a meal. These data suggest that individuals with less sensitivity to insulin may fail to shift brain networks away from reward and toward cognitive control following a meal. This altered feedback loop could promote overeating and obesity.